Human and murine class I and class II molecules are isolated and their primary structure analyzed. The goal of these studies is to gain an understanding of their function and antigenic properties in molecular terms as well as to gain knowledge of their evolutionary relationships. Structural analyses of D region molecules of the q haplotype have shown the existence of three unique gene-products - Dd, Ld and Rd. These molecules are more closely related than any previously described H-2 molecules suggesting that they have arisen by relatively recent gene duplications. In addition, extension amino acid sequence information has been acquired for the H-2KK molecule allowing comparison to previously determined sequences of other class I molecules. In the case of human class I molecules, the location of structural differences in HLA-A3 molecules recognized as being different by cytotoxic T cells is in progress both at the protein and gene level. Studies on murine Ia molecules are seeking to prove whether or not two structurally distinct IE molecules are present in the mouse. In addition, the nature of the structural differences between wild type IA molecules (Iakw12a) and IAk molecules are being determined. These molecules are virtually indistinguishable serologically, but are readily distinguishable by MLR.